Salvage Efforts Research Articles

Mitochondrial pyruvate import is a metabolic vulnerability in androgen receptor-driven prostate cancer

Specific metabolic underpinnings of androgen receptor (AR)-driven growth in prostate adenocarcinoma (PCa) are largely undefined, hindering the development of strategies to leverage the metabolic dependencies of this disease when hormonal manipulations fail. Here we show that the mitochondrial pyruvate carrier (MPC), a critical metabolic conduit linking cytosolic and mitochondrial metabolism, is transcriptionally regulated by AR. Experimental MPC inhibition restricts proliferation and metabolic outputs of the citric acid cycle (TCA) including lipogenesis and oxidative phosphorylation in AR-driven PCa models. Mechanistically, metabolic disruption resulting from MPC inhibition activates the eIF2α/ATF4 integrated stress response (ISR). ISR signaling prevents cell cycle progression while coordinating salvage efforts, chiefly enhanced glutamine assimilation into the TCA, to regain metabolic homeostasis. We confirm that MPC function is operant in PCa tumors in-vivo using isotopomeric metabolic flux analysis. In turn, we apply a clinically viable small molecule targeting the MPC, MSDC0160, to pre-clinical PCa models and find that MPC inhibition suppresses tumor growth in hormone-responsive and castrate-resistant conditions. Collectively, our findings characterize the MPC as a tractable therapeutic target in AR-driven prostate tumors.

FURTHER INSIGHTS INTO PALEOINDIAN USE OF THE POWARS II RED OCHER QUARRY (48PL330), WYOMING

We report major new insights from recent research at the Powars II Paleoindian red ocher quarry (48PL330). We salvaged more than 7,000 artifacts from Powars II between 2014 and 2016 by screening redeposited sediment from the talus slope below the intact portion of the site. Clovis artifacts dominate the diagnostic artifact assemblage, including 53 Clovis points, 33 preforms, and artifacts associated with a previously unrecognized blade core industry. We report the first radiocarbon dates from the site, determined from dating bone tools, which indicate Cody-aged use (ca. >10,000 cal BP). Further, salvage efforts discovered a previously unknown toolstone source from which many of the Clovis artifacts were produced. The Powars II Clovis points most resemble early Paleoindian points from the far Northern Plains and were likely both produced and discarded in the red ocher quarry after hunting, as evidenced by preform production and the presence of impact fractures on many used points. Given these production and discard patterns, Powars II holds some of the best evidence archaeologists currently have for Paleoindian ritualism related to hunting.

Magnitude of Soft-Tissue Defect as a Predictor of Free Flap Failures: Does Size Matter?

To examine the relationship between the magnitude of soft-tissue defect and the risk of free-flap and limb-salvage complications/failures. Retrospective cohort. Level I Trauma Center. One hundred twelve patients with free tissue transfers between January 2009 and June 2015. A standardized approach using a consistent team of 2 orthopaedic microvascular surgeons was used for each free-flap reconstruction. Soft tissue defect size, total or partial flap failure, and unplanned reoperations. Of 112 free-flap reconstructions, 57 complications occurred in 43-cases (38%) including 5 total flap failures (4.5%), 7 partial flap failures (6%), and 8 early (7%) and 38 delayed complications (33%). There was a significant correlation between the large defect size (≥200 cm) and partial/total flap failure (n = 80, P = 0.023). There was also a significant correlation between large soft tissue defect size and any complication that is, total or partial failure and early or delayed unplanned return to the operating room (n = 80, P = 0.002). Of the flaps used, multivariate analysis revealed that latissimus flaps had higher odds for failure. Soft-tissue defect size ≥200 cm can be associated with a higher rate of total or partial flap failure and any complication in acute trauma setting, which may be due to a larger zone of injury, a higher level of difficulty in achieving complete debridement, and a more complex microvascular dissection. Current and future efforts will need to continue to focus on risk stratification for limb salvage efforts because an accurate assessment of risk is important to the patient, health care provider, and the health care system in general. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Salvage along the Red River: The Red Cox (3LA18) Site and its Place on the Caddo Landscape

The Red Cox (3LA18) site is located in Lafayette County, Arkansas along the Red River. As recounted in his weekly report of April 9, 1975, Dr. Frank Schambach received word that the site was being directly impacted by land leveling machinery. Salvage efforts collected the remains from the floor of a burned Caddo farmstead structure. Remains include ceramic sherds, carbonized corn kernels, acorn nutmeat and nutshells, burned wood fragments, and bits of daub. In this paper, we present the results of a recent analysis of the materials and situate the farmstead within the Red River landscape during a period shortly after Haley (ca. A.D. 1200 - 1400) phase and into the early part of the Belcher (ca. A.D. 1400 - 1700) phase.

Burned Record Imaging at NARA

On July 12, 1973 a devastating fire at the National Personnel Records Center (NPRC) in St. Louis destroyed approximately 16-18 million Army and Air Force Official Military Personnel Files (OMPFs) from the early and mid-twentieth century – 80% of the total military personnel records of this time period. During the salvage efforts following the fire approximately 6.5 million records were recovered. OMPFs are commonly requested by government agencies and individual citizens for the purpose of obtaining veterans' benefits and researching personal or family histories. In 2015 a multiple spectrum imaging workflow was put in place to digitize the most heavily damaged records as they are requested – records at a condition level that formerly prevented their being accessed by requestors. Digital versions are provided in lieu of originals for these requests. To counter information loss in charred record pages, the National Archives and Records Administration (NARA) utilizes infrared imaging as part of the process. This paper describes the production imaging project now underway, with particular attention paid to the unique requirements of photographing brittle and charred originals. The author shares information about the overall strategy, methods to prepare records for imaging and a photographic technique to maximize content recovery.

The impact of foot ulceration and amputation on mortality in diabetic patients. I: From ulceration to death, a systematic review.

A great deal of emphasis, clinical and financial, is placed on limb salvage efforts in diabetic patients suffering from lower extremity ulceration. This is because of the impression that amputation in such patients may be a proximal cause of death. While amputation is certainly a negative clinical outcome, it is not entirely clear that it causes death. In this systematic review, we examine the available literature to attempt to understand the role that the ulceration itself may play in mortality. In brief, we searched for human studies in OVID, CINAHL and the COCHRANE CENTRAL DATABASE from 1980 to 2013, looking for articles related to ulcer or wound of the foot, in patients with diabetes or peripheral vascular disease, and death. We looked for articles with 5 years of follow-up, or Kaplan-Meier estimates of 5-year mortality, and excluded reviews and letters. Articles were assessed for quality and potential bias using the Newcastle-Ottawa scale. We find that while the patient populations studied varied widely in terms of demographics and comorbidities, limiting generalisability, 5-year mortality rates after ulceration were around 40%. Risk factors for death commonly identified were increased age, male gender, peripheral vascular disease and renal disease.

Volumetric muscle loss: persistent functional deficits beyond frank loss of tissue.

Open fracture is a common occurrence in civilian and military populations. Though great strides have been made in limb salvage efforts, persistent muscle strength deficits can contribute to a diminished limb function after the bone has healed. Over the past decade, a growing effort to establish therapies directed at de novo muscle regeneration has produced several therapeutic approaches. As this effort progresses and as therapies reach clinical testing, many questions remain regarding the pathophysiology of the volumetric loss of skeletal muscle. The current study demonstrates, in a rat "open fracture" model, that the volumetric loss of skeletal muscle results in persistent functional deficits that are dependent on muscle length and joint angle. Moreover, the injured muscle has an increased stiffness during passive stretch and a reduced functional excursion. A case study of a patient with an open type III tibia fracture resulting in volumetric muscle loss in the anterior and posterior compartment is also presented. Eighteen months after injury and tibia healing, persistent functional deficits are apparent with many of the same qualities demonstrated in the animal model. Muscle architectural adaptations likely underlie the altered intrinsic functional characteristics of the remaining musculature.

Raising titans: How do you salvage a mega-ship?

Salvage efforts were pushed to the limit after the Costa Concordia ran aground – and things could get harder as a new generation of monster vessels takes to the high seas

Foot reconstruction using a serratus anterior muscle flap from the same donor site after failure of a thoracodorsal artery perforator flap

The free flap failure rate for the lower extremities is high, which adversely affects limb salvage efforts. In this article, we report a case of failure of a thoracodorsal artery perforator flap, which was simultaneously reconstructed with a serratus anterior muscle flap from the same donor site. A 56-year-old male patient had infected wound for 3 months due to Achilles tendon rupture. We reconstructed the defect using a thoracodorsal artery perforator flap. However, 2 days after the operation, we found the congested flap. We were obliged to discard the whole flap and harvested a serratus anterior muscle flap from the same donor site. The patient's foot healed uneventfully. After flap failure, the use of a second free flap from the same donor site may be an effective and safe procedure in specific cases.

‘Récupérez!’ The German Origins of French Wartime Salvage Drives, 1939–1945

AbstractThis article examines the origins, implementation and results of salvage drives carried out in wartime France from 1939 to 1945. In post-war accounts – including memoirs and local histories of the occupation – these salvage drives were understood simply as wartime frugality, a logical response to wide-spread shortages. Yet a careful study of the records of both the French Ministry of Armaments and Vichy's Service de la Récupération et de l'Utilisation des Déchets et Vieilles Matières combined with municipal and departmental sources reveals that these salvage drives were heavily influenced by Nazi German practices. From 1939 to 1940, even though French propaganda had previously ridiculed Nazi German salvage drives as proof of economic weakness, officials at the Ministry of Armaments emulated Nazi Germany by carrying out salvage drives of scrap iron and paper. After the fall of France, this emulation became collaboration. Vichy's salvage efforts were a conjoint Franco-German initiative, organised at the very highest levels of the occupation administration. Drawing on the experience of Nazi German salvage experts, Vichy officials carried out the salvage drives according to German models. Nevertheless, they carefully hid the German origins of the campaign from the chain of departmental prefects, mayors, Chambers of Commerce and youth leaders who organised the local drives and solicited participation by evoking French patriotic sentiment. After the liberation of France in 1944, the French Provisional Government renamed but otherwise maintained the Vichy-created salvage organisations and continued to oversee the collection of scrap iron, paper, rags, glass and bones until 1946. At that point, the government largely relinquished control of the salvage industry.

Boston Bombings

The Boston bombing incident was a recent civilian mass casualty terrorist event that demonstrated effective transfer of the lessons of combat casualty care to inform effective civilian medical care. Thirty-nine patients were seen at Brigham and Women's Hospital and thirteen patients received emergency surgery in the first few hours after the event. The subsequent management, total hospital days 181, total number of operative procedures 72, and discharging service listing of these thirteen patients illustrate the intensive surgical resources necessary after a civilian bomb attack. Plastic surgery played a role in the multidisciplinary collaboration of the limb salvage efforts and this role can inform the importance of other plastic surgery contributions within mass casualty surgical management. We believe that prepositioned collaborative relationships of plastic surgery, vascular surgery, trauma surgery and orthopedic surgery may offer a model of collaboration for limb salvage that can be applied in military and mass casualty medical care if resources permit. In this attack, effective use of tourniquets was implemented by prehospital medical providers that saved lives and limbs and these actions reaffirm the important lessons learned from combat casualty care. Unfortunately, it is likely that more centers will deal with similar events in the future and it is imperative that we as a community of providers take what lessons we can from battlefield medicine and that we collectively prepare for and engage this future.

Conservation Status of an Endemic Kinosternid, Kinosternon sonoriense longifemorale, in Arizona

Abstract The Sonoyta mud turtle (Kinosternon sonoriense longifemorale) is a member of the unique desert riparian fauna isolated along the Rio Sonoyta watershed in northern Sonora, Mexico, and southern Arizona. This subspecies occupies six sites along the Rio Sonoyta, a pool at Quitovac in Sonora, and one pond at Quitobaquito Springs in Organ Pipe Cactus National Monument in Arizona. Since the mid-1980s, population estimates for the US population have ranged from 39–153 individuals. In 2006–2007, the human-made Quitobaquito Pond began losing water, and discussions were held concerning the fate of the turtles. During three salvage efforts all Sonoyta mud turtles encountered were captured and transported to temporary holding facilities. Because the minimum number of turtles needed for re-establishment was unknown, we conducted a Population Viability Analysis (PVA) to determine the number of Sonoyta mud turtles that should be held in an assurance colony. Results from both our PVA and previous work suggested t...

"Nations Will Not Survive Without Their Cultural Heritage" Karol Estreicher, Polish Cultural Restitution Plans and the Recovery of Polish Cultural Property from the American Zone of Occupation

Abstract As the war and Nazi occupation intensified, the registration of cultural losses became a considerable component of salvage efforts and laid the foundation for postwar restitution of Polish movable cultural property. Cultural losses registration was a coordinated effort by the Polish government-in-exile in London and the Polish underground government in Nazi-occupied Poland. It involved hundreds if not thousands of curators, art scholars, librarians, university professors and students, museum employees, and couriers. Nevertheless, one individual emerged as the leader of Poland’s efforts to publicize its cultural losses and lobby for the return of Polish cultural property looted by the Nazis. Passionate about Poland’s cultural assets, Karol Estreicher, an art historian and bibliographer from the Jagiellonian University in Kraków, would not rest until Poland had recovered its most important treasures, including the Veit Stoss (Wit Stwosz) altarpiece from St. Mary’s Church in Kraków. The article examines Polish cultural losses registration and plans for the restitution of cultural property and compensation for Poland’s cultural losses. Polish restitution efforts in the American occupation zone are discussed in the context of American cultural restitution and reparations policy as formulated by the Roberts Commission and the U.S. State Department. Finally, the question of using cultural assets as war reparations is examined with respect to Polish plans for reparation claims of German cultural property.

Benefit of immediate revascularization in women with critical limb ischemia in an intention-to-treat analysis

Evidence for the best treatment strategy in women with critical limb ischemia (CLI) is limited and controversial with studies contradicting each other. Therefore, we determined the benefit of immediate revascularization compared to medical therapy (MT) with optional delayed revascularization in men and women with CLI. This cohort study with follow-up at 2, 6, and 12 months was conducted in a consecutive series of 356 patients (41% women) presenting with 394 critically ischemic limbs. In this intention-to-treat study, 292 limbs were assigned to immediate revascularization by either surgical (81 limbs) or endovascular techniques (211 limbs) at the time of first presentation with CLI, whereas MT as first-line therapy was administered in 102 limbs with CLI. Primary outcome measures were overall and amputation-free survival. Cox-regression models adjusted for 10 baseline characteristics following Kaplan-Meier Survival estimates were performed. Women with CLI were significantly older than men (P < .001), had higher systolic blood pressure (P = .03) and cholesterol levels (P = .04), but less women presented with renal failure (P = .03) and less were smokers (P < .001). In women, but not in men, immediate revascularization was associated with a prolonged overall survival (hazard ratio [HR], 2.37; 95% confidence interval [CI], 1.29-4.34; P = .01) and amputation-free survival compared to MT (HR, 2.11; 95% CI, 1.30-3.43; P = .01), irrespective of whether surgery or percutaneous transluminal angioplasty (PTA) was performed (not significant). Except for overall survival (HR, 2.14; 95% CI, 0.95-4.82; P = .07), outcomes were not significantly changed after Cox regression analysis. Women presenting with CLI profit from immediate revascularization therapy, irrespective of revascularization technique used and despite advanced age and differences in other cardiovascular risk factors. Thus, our data suggest aggressive and early limb salvage efforts in women with CLI.

Clinical and epidemiological features of human rabies cases in the Philippines: a review from 1987 to 2006

Rabies viral infection causes a fatal encephalomyelitis. In humans, classic features include hydrophobia, aerophobia, hypersalivation, agitation, and neurological symptoms. In the Philippines, canine rabies contributes to a significant burden of human disease. We retrospectively reviewed the medical records of 1839 patients admitted to San Lazaro Hospital, Manila, Philippines between 1987 and 2006, with a clinical diagnosis of rabies. We used the World Health Organization case definition for clinical rabies, which is defined by the presence of hydrophobia. Male patients outnumbered females by 2.2 to 1 and twice the number of adults were affected compared with children. Most patients were indigent. Dog bites occurred more than cat bites (97.1% vs. 2.9%) and most cases were caused by a single bite (86.2%), compared to multiple bites (8.7%). Bites to the face, head, and neck led to shorter incubation times, yet the incubation period varied, with most cases (42.7%) occurring in the bracket of 91-365 days post-exposure. Clinical symptoms included hydrophobia in all cases, as per our case definition, and aerophobia in 95.5%; only 9.4% had fever, 9.2% exhibited restlessness, and 6.7% exhibited hypersalivation. Localized neurological symptoms included pain (4.1%), numbness (2.6%), and itching (2.3%). None of the patients received appropriate post-exposure prophylaxis (PEP). This study examines the largest cohort of rabies patients reported to-date. Better understanding of clinical disease manifestations may help in salvage efforts to save patients with rabies. Knowledge of epidemiological factors will improve preventative efforts to reduce suffering from rabies.

The Costs of Diabetic Foot

In 2007, the treatment of diabetes and its complications in the United States generated at least $116 billion in direct costs; at least 33% of these costs were linked to the treatment of foot ulcers. Although the team approach to diabetic foot problems is effective in preventing lower-extremity amputations, the costs associated with implementing a diabetic-foot-care team are not well understood. An analysis of these costs provides the basis for this report. Diabetic foot problems impose a major economic burden, and costs increase disproportionately to the severity of the condition. Compared with diabetic patients without foot ulcers, the cost of care for those with foot ulcers is 5.4 times higher in the year after the first ulcer episode and 2.8 times higher in the second year. Costs for treating the highest-grade ulcers are 8 times higher than are those for treating low-grade ulcers. Patients with diabetic foot ulcers require more frequent emergency department visits and are more commonly admitted to the hospital, requiring longer lengths of stay. Implementation of the team approach to manage diabetic foot ulcers in a given region or health-care system has been reported to reduce long-term amputation rates 62% to 82%. Limb salvage efforts may include aggressive therapy such as revascularization procedures and advanced wound-healing modalities. Although these procedures are costly, the team approach gradually leads to improved screening and prevention programs and earlier interventions and, thus, seems to reduce long-term costs. To date, aggressive limb preservation management for patients with diabetic foot ulcers has not usually been paired with adequate reimbursement. It is essential to direct efforts in patient-caregiver education to allow early recognition and management of all diabetic foot problems and to build integrated pathways of care that facilitate timely access to limb salvage procedures. Increasing evidence suggests that the costs of implementing diabetic foot teams can be offset in the long term by improved access to care and reductions in foot complications and amputation rates.

The costs of diabetic foot: The economic case for the limb salvage team

In 2007, the treatment of diabetes and its complications in the United States generated at least $116 billion in direct costs; at least 33% of these costs were linked to the treatment of foot ulcers. Although the team approach to diabetic foot problems is effective in preventing lower extremity amputations, the costs associated with implementing a diabetic foot care team are not well understood. An analysis of these costs provides the basis for this report. Diabetic foot problems impose a major economic burden, and costs increase disproportionately to the severity of the condition. Compared with diabetic patients without foot ulcers, the cost of care for patients with a foot ulcer is 5.4 times higher in the year after the first ulcer episode and 2.8 times higher in the second year. Costs for the treatment of the highest-grade ulcers are 8 times higher than for treating low-grade ulcers. Patients with diabetic foot ulcers require more frequent emergency department visits, are more commonly admitted to hospital, and require longer length of stays. Implementation of the team approach to manage diabetic foot ulcers within a given region or health care system has been reported to reduce long-term amputation rates from 82% to 62%. Limb salvage efforts may include aggressive therapy, such as revascularization procedures and advanced wound healing modalities. Although these procedures are costly, the team approach gradually leads to improved screening and prevention programs and earlier interventions, and thus seems to reduce long-term costs. To date, aggressive limb preservation management for patients with diabetic foot ulcers has not usually been paired with adequate reimbursement. It is essential to direct efforts in patient-caregiver education to allow early recognition and management of all diabetic foot problems and to build integrated pathways of care that facilitate timely access to limb salvage procedures. Increasing evidence suggests that the costs for implementing diabetic foot teams can be offset over the long-term by improved access to care and reductions in foot complications and in amputation rates.

Management response to one insect pest may increase vulnerability to another

Summary 1. Large-scale insect outbreaks provide an ideal system to examine the cascade of ecological effects of disturbance regimes across forested landscapes. A major outbreak of the mountain pine beetle Dendroctonus ponderosae continues to exert landscape-level mortality across forests of lodgepole pine Pinus contorta var. latifolia. in western Canada. This outbreak, exacerbated in part by fire suppression and climate change, has affected more than 14 million ha of merchantable forest. Salvage and reforestation efforts are currently underway at landscape-level scales. An emerging concern is the migration of Warren root collar weevil Hylobius warreni from stands with a reduced host pool, i.e. those with a high per cent of mature, dead lodgepole pine, into young, replanted stands, resulting in significant levels of mortality to juvenile trees. 2. The impact of Warren root collar weevil in stands of young trees (9–11 years of age) replanted after salvage harvesting was examined in nine cutblocks (areas delineated for commercial timber harvest, c. 1 km in diameter). All cutblocks, sampled across the central interior of British Columbia, were located next to unsalvaged, mature stands. 3. Field data and aerial surveys revealed higher tree mortality from Warren root collar weevils along cutblock perimeters adjacent to unsalvaged, mature stands. Mortality decreased with increasing distance from the edge of the cutblocks. Additional mortality along these gradients was associated with increasing per cent of pine in the mature stand; more-so if the pine was dead. Moreover, the gradient of mortality became more pronounced with time as mountain pine beetle had attacked the adjacent mature stands. Weevils attacked the largest trees within the replanted cutblocks. 4. These gradients of tree mortality suggest migration of Warren root collar weevils from unsalvaged mature stands into adjacent replanted forests most probably in search of food. 5. Synthesis and applications. This study demonstrates how a management response to a large insect outbreak, itself mediated by anthropogenic factors, can predispose reforested stands to additional, unanticipated threats from other insects. Reforestation strategies following outbreaks of mountain pine beetle may need to include harvesting larger salvage blocks to minimize edge effects and reduce mortality from Warren root collar weevils. Moreover, the inclusion of deciduous non-host tree stock in planting mixes might reduce insect movement and limit tree mortality because of Warren root collar weevils.

INTERTIDAL ZONE OIL RECOVERY FROM THE BURIED DERELICT S.S. CATALA

ABSTRACT Built in Scotland as a Union Steamship Company tramper in 1925, the S.S. Catala plied the coast of British Columbia for decades before ending her sailing career as a floating hotel in Ocean Shores, Washington. In 1965 a fierce Pacific storm capsized the 229’ riveted steel-hulled vessel at her moorings transforming a real estate developer'S dream into a local attractive nuisance. The casualty occurred at Damon Point, a land spit that has since become a State Park and is one of the coast'S richest migratory waterfowl habitats as well as the nesting ground for two federal and state-listed threatened birds. Multiple salvage efforts had failed before the derelict'S superstructure was cut away and the hull buried in the mid-80'S. In the spring of 2006 a beachcomber discovered black oil within the Catala'S rusted remains setting-off a Washington State Department of Ecology driven effort to remediate the wreck before the winter storm season created a catastrophic persistent oil release. Time was short: site access could not begin until August when the threatened birds vacated the spit; the contractor had to withdraw by the end of September when the site became vulnerable to ocean storm surges. Regulatory compliance was complicated: Ecology had to win fast-track permits from five separate agencies before they could authorize their contractor, Global Diving &amp; Salvage, to begin work. Engineering was challenging: heeled over and buried in the intertidal zone, the Catala'S keel was 26’ below grade; a robust sheet pile cell had to be constructed to provide worker safety from unstable soils and manage water inflow. Despite these conditions the project team was able to safely remove over 30,000 gallons of bunker oil from the ship delivering to the State of Washington a striking example of the benefits of a pro-active derelict vessel response. This case study will discuss the technical and managerial process by which this intertidal site was remediated.

Invited Commentary

Dr Shander discloses a financial relationship with Novo Nordisk. Dr Shander discloses a financial relationship with Novo Nordisk. Level 1 evidence is seriously lagging behind the wide off-label use of recombinant activated factor VII (rFVIIa) in the control of massive or insurmountable bleeding. Dunkley and colleagues [1Dunkley S. Phillips L. McCall P. et al.Recombinant activated factor VII in cardiac surgery: experience from the Australian and New Zealand Haemostasis Registry.Ann Thorac Surg. 2008; 85: 836-844Abstract Full Text Full Text PDF PubMed Scopus (51) Google Scholar] have made a commendable effort in gathering and analyzing the data on nonhemophilia cardiac surgery cases with critical bleeding treated with rFVIIa from a large multicenter registry with financial support from Novo Nordisk. The study faces limitations, many of which are shared with other registries; lack of a control group is perhaps the biggest obstacle in interpreting the data, given the complicated nature of cardiac surgery and the numerous confounding variables and heterogeneous practices. For instance, 15 cases received platelets, fresh frozen plasma (FFP) or cryoprecipitate, but no red blood cells prior to rFVIIa. As an alternative to control, authors have resorted to comparing measurements before and after rFVIIa administration. However, observed improvements can be the result of collective salvage efforts rather than rFVIIa alone. In addition, data on 87% of the cases have been retrospectively collected, which raises the questions of accuracy, especially for response to treatment. With some cases dating back more than 4 years, the potential memory lapse combined with the possible bias toward the treatment can result in inaccuracies. Apart from the old cases, the subjective reporting of this outcome is of significant concern. Although the authors argue that this measure concurs with mortality rates, objective measurements (such as chest tube drainage) would have been more desirable. Finally, lack of set times for measuring blood parameters before and after giving rFVIIa could substantially obscure the causal relationship between the measured values and the treatment. In a registry, bias can be introduced at many levels including data collection, submission, and analysis. The authors have taken appropriate countermeasures (ie, participating hospitals were required to submit all cases and their adherence was audited). The observed median dose in this study was very close to the dose used in hemophilia patients as well as off-label cases. Interestingly, dose was not associated with outcomes, suggesting the possibility of lower doses being as effective (or less likely, the drug not being effective at all and all the observed improvements being due to other treatments). The observed thromboembolic adverse event rate of 7% in this study is close to the previously reported rates, which is of concern. This rare but significant complication would be acceptable providing rFVIIa had a demonstrable higher benefit. In summary and within constrains of a registry, this study serves to highlight some of the issues facing future trials on rFVIIa, such as defining outcomes and accounting for heterogeneity in practices while suggesting an acceptable safety profile. Although the present study provides a valuable insight, ongoing and future controlled trials will hopefully provide the much needed higher quality evidence for the “off-label” use of rFVIIa. Recombinant Activated Factor VII in Cardiac Surgery: Experience From the Australian and New Zealand Haemostasis RegistryThe Annals of Thoracic SurgeryVol. 85Issue 3PreviewData from the Australian and New Zealand Haemostasis Registry (ANZHR) were used to report on the efficacy, mortality, and outcomes of a cohort of cardiac surgical cases receiving recombinant activated factor VII (rFVIIa). Full-Text PDF